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Extracellular Vesicle Protein and MiRNA Signatures as Biomarkers for Post-Infectious ME/CFS Patients.
Martina Seifert1,2,3, Johannes Schäfers1, Fiona F Douglas1
1Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, 10117 Berlin, Germany.
International Journal of Molecular Sciences
|March 14, 2026
Summary
Researchers identified novel biomarkers in extracellular vesicles (EVs) for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). These EV cargo differences, including specific proteins and microRNA, show promise for diagnosing ME/CFS and stratifying patients.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) presents diagnostic challenges due to unknown pathophysiology.
- Extracellular vesicles (EVs) are implicated in disease by carrying specific molecular signatures.
Purpose of the Study:
- To identify novel protein and microRNA (miRNA) biomarkers in plasma EVs for diagnosing ME/CFS in female patients.
- To compare EV cargo in post-COVID-19 ME/CFS and other post-infectious ME/CFS cases against healthy controls.
Main Methods:
- Plasma EVs were isolated using size-exclusion chromatography and characterized.
- Proteomic profiling and small RNA sequencing were performed on EV cargo.
- Quantitative PCR (qPCR) validated miRNA findings.
Main Results:
- Proteomic analysis revealed altered levels of hemoglobin subunit alpha and insulin-like growth factor-binding protein acid labile subunit in ME/CFS patient EVs.
- Significant downregulation of hsa-let-7b-5p was observed in EVs from post-COVID-19 ME/CFS patients.
- Reduced hsa-let-7b-5p correlated with increased fatigue, pain, and immune activation.
Conclusions:
- EV cargo proteins (hemoglobin subunit alpha, IGFBP7) and miRNA (hsa-let-7b-5p) are potential biomarkers for ME/CFS diagnosis.
- These biomarkers may aid in stratifying ME/CFS patients for personalized treatment approaches.

